A novel compound inhibits reconstituted high-density lipoprotein assembly and blocks nascent high-density lipoprotein biogenesis downstream of apolipoprotein AI binding to ATP-binding cassette transporter A1-expressing cells.

ABSTRACT:

Objective

Nascent high-density lipoprotein (HDL) particles form from cellular lipids and extracellular lipid-free apolipoprotein AI (apoAI) in a process mediated by ATP-binding cassette transporter A1 (ABCA1). We have sought out compounds that inhibit nascent HDL biogenesis without affecting ABCA1 activity.

Methods and results

Reconstituted HDL (rHDL) formation and cellular cholesterol efflux assays were used to show that 2 compounds that bond via hydrogen with phospholipids inhibit rHDL and nascent HDL production. In rHDL formation assays, the inhibitory effect of compound 1 (methyl 3α-acetoxy-7α,12α-di[(phenylaminocarbonyl)amino]-5β-cholan-24-oate), the more active of the 2, depended on its ability to associate with phospholipids. In cell assays, compound 1 suppressed ABCA

SUBMITTER: Lyssenko NN 

PROVIDER: S-EPMC3197940 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature